In The Field

AACR: The return of cox-2 inhibitors

Today’s plenary session on ‘late-breaking clinical trials’ offered up a few new promising phase III trial results for the prevention of colorectal cancer.

The first was an update on a kind of cox-2 inhibitor called celecoxib (marketed as Celebrex). You may remember the cox-2 inhibitors — they’re a class of anti-inflammatory drugs that were the center of a scandal a few years ago when it turned out they carried increased risk of cardiovascular side effects, such as heart attacks or stroke. Most of the scandal (and accusations of suppressed negative data) revolved around rofecoxib, better known as “Vioxx”, which was subsequently pulled from the market. Celecoxib is still available but carries the dreaded black-boxwarning. (The black box is the FDA’s strongest warning, and is the last stop before yanking a drug off the market entirely.)

But celecoxib had shown promise for preventing colorectal cancer in those at high risk for the disease, and I’ve heard it said on several occasions that the negative press about the drugs’ possible cardiovascular harm unfairly restricted use of what could have been a valuable cancer preventative. Today, Monica Bertagnolli of Brigham and Women’s Hospital in Boston reported that the protective effects of celecoxib have persisted in patients that stopped taking the drug 1.5 years ago, when the study was halted due to the realization that celecoxib posed a cardiovascular risk.

Bertagnolli’s data, summarized below, allay two fears about the use of celecoxib as a cancer preventative. First, some had hypothesized that the anti-inflammatory drug was not preventing the formation of abnormal growths, called adenomas, but was simply delaying their detection. These critics hypothesized that once patients stopped taking the drugs, the cancer would appear in full force, no different from placebo. But the data argue against that –adenomas were still reduced well after patients abandoned the drugs. A few stats:

Number of patients in the study:

Average length of celecoxib treatment: 3.5 years

Date that the treatment was halted due to increased cardiovascular toxicity: December 2004

Percent reduction in the occurrence of adenomas in who took 200mg celecoxib, twice a day: 14%

Reduction in ‘advanced’ adenomas at three years: 57% reduction

Reduction in advanced adenomas at five years (1.5 years after treatment stopped): 41%

Bertagnolli’s data also address the risk of cardiovascular side effects. When her data was stratified according to pre-existing cardiovascular risk factors (things like diabetes, smoking, high blood pressure, etc), she found those who did not carry these risk factors were much less likely to experience the cardiovascular side-effects of celecoxib. The data here are a little weak on this point, she acknowledged, because 84% of her patients had at least one risk factor, leaving her with relatively small numbers in the “no risk” category. But overall, the results suggested that celecoxib may be beneficial in those with a risk of colorectal cancer but with no preexisting cardiovascular risk factors.


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